Is DST p.Asn4244Ser (c.12731A>G) pathogenic?

DST p.Asn4244Ser (c.12731A>G) is classified Uncertain significance in DST (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-18). Ultra-rare (popmax 0.0194%, sas); Associated with hereditary sensory and autonomic neuropathy type 6.

What condition is associated with DST p.Asn4244Ser (c.12731A>G)?

DST p.Asn4244Ser (c.12731A>G) is associated with hereditary sensory and autonomic neuropathy type 6, epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (ClinVar).

How common is DST p.Asn4244Ser (c.12731A>G) in the general population?

DST p.Asn4244Ser (c.12731A>G) is ultra-rare (popmax 0.0194%, sas) (gnomAD).

DST p.Asn4244Ser

Q: How is Hereditary sensory and autonomic neuropathy type 6 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.12731A>G · rs200672626 · VCV964912

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0194%, sas)

Conditions

hereditary sensory and autonomic neuropathy type 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.041	moderately benign-leaning
Splicing
SpliceAI	Δ0.85	acceptor gain · deltas
Pangolin	Δ0.39	gain · loss 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -3.1	GERP -4.5
Regional constraint	o/e 0.90	unconstrained · MANE · 46 kb · p 5.7e-05 · regional, not allelic
Overall
CADD	18.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0194% South Asian · 17/87,496 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.0108% 172/1,588,776 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0194%	5,147
Middle Eastern	0.0165%	6,054
European (non-Finnish)	0.0118%	8,447
Remaining individualsnot grpmax-eligible	0.0081%	12,343
Finnishnot grpmax-eligible	0.00794%	12,587
African / African-American	0.00537%	18,634
East Asian	0.00452%	22,118

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DST
Protein: p.Asn4244Ser
Coding: c.12731A>G
MANE Select: NM_001374736
dbSNP: rs200672626
Type: single nucleotide variant
Location: chr6:56592354 (GRCh38)
Gene constraint: LOEUF 0.297 · pLI 1.00 (gnomAD)

Full DST gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary sensory and autonomic neuropathy type 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency

For Hereditary sensory and autonomic neuropathy type 6 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DST p.Asn4244= Uncertain significance ★ same residue
DST c.22959+1G>A Likely pathogenic ★★ same condition
DST p.Arg1512Ter Pathogenic/Likely pathogenic ★★ same condition
DST p.Arg1696Ter Pathogenic/Likely pathogenic ★★ same condition
DST p.Arg22Ter Likely pathogenic ★★ same condition
DST p.Arg7329Ter Pathogenic ★★ same condition
DST p.Cys1828Ter Pathogenic/Likely pathogenic ★★ same condition
DST p.Gln1124Ter Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dst-p-asn4244ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown